INVESTIGADORES
TARAVINI Irene Rita Eloisa
congresos y reuniones científicas
Título:
New neuroprotective role of modafinil against methamphetamine acute toxic effects in mice.
Autor/es:
RAINERI M; GOITIA B; TARAVINI I; PESKIN V; GIORGERI S; URBANO F; BISAGNO V
Lugar:
Washington, DC
Reunión:
Congreso; 41st Annual Meeting of the Society for Neuroscience; 2011
Institución organizadora:
Society for Neuroscience
Resumen:
Modafinil
(MOD) is an antinarcoleptic drug that is also being used off-label to treat
psychostimulant addiction. Methamphetamine (METH) intake produces deleterious
effects on brain function. The objective of the present study was to explore
the neuroprotective role of MOD on METH neurotoxic effects. Mice were treated
either with a METH single i.p. injection (2 or 7 mg/kg) or with a binge dosing
protocol of METH (3 i.p. injections of 7mg/kg, 3 h apart) co-administrated with
MOD (2 injections of 180 or 2 injections of 90 mg/kg, i.p., 1 h before first
and third METH injection). Acute METH (7mg/kg) administration induced
hyperlocomotion (p<0.0001, ANOVA) and increased continuous sniffing compared
to MOD and saline/vehicle values (p<0.05, ANOVA). Acute MOD increased
locomotor activity in a dose dependent manner (p<0.0001, ANOVA) without
enhancing stereotyped behavior. Groups receiving the combination of MOD and
METH exhibited locomotor activity values similar to those of saline/vehicle
groups and enhanced stereotyped behavior (i.e., increased time spent in
continuous sniffing), (p<0.05, ANOVA). Six days after METH binge,
spontaneous locomotor activity was recorded and reduced distance traveled was
observed in METH treated animals (p<0.0001, ANOVA). MOD pre-treatment was
not able to counteract this effect. Striatal dopamine, HVA, DOPAC content
(measured by HPLC) and TH immunoreactivity were decreased in METH treated
animals (p<0.01, ANOVA) while MOD+METH groups showed similar values compared
to saline/vehicle groups (measured 6 days after last METH injection). Our
results suggest a possible protective role of MOD against METH acute toxicity.